The Children's National Medical Center (CNMC), in collaboration with Georgetown University Medical Center (GU) and the George Washington University School of Medicine and Health Sciences (GWU), is submitting a competitive renewal for its Mental Retardation and Developmental Disabilities Research Center (MRDDRC). This center focuses on developmental and cellular aspects of brain development and dysfunction and on the molecular basis of genetic diseases causing intellectual and other developmental disabilities. The 84 NIH/NSF funded grants that form the investigator group for the MRDDRC have annual direct costs of more than $21 million, over $7 million from NICHD. The projects cover 23 of the 31 areas of focus in the MRDDRC RFA: HD-05-030. A total of 69 faculty members are affiliated with the MRDDRC as Center Investigators. These faculty represent 23 departments/divisions from the collaborating institutions. We propose to support an Administrative and 5 scientific cores: Molecular Genetics, Proteomics and Biochemical Analysis Core (MGPBAC);Cellular Imaging Core (Cl);Neuroimaging Core: Neurobehavioral Evaluation Core (NEC);and Biostatistics and Informatics Core (BIC). The Director of the MRDDRC, Mark L. Batshaw, M.D., was previously the founding Director of the Children's Hospital of Philadelphia MRDDRC (1990-1998). He will also direct the Administrative Core that functions as the hub of the Center, providing strategic planning, financial oversight and administrative services to cores and users. MGPBAC provides access to and training in advanced molecular biologic technologies including expression microarrays, quantitative PCR and automated DNA sequencing, proteomic technology and biochemical analysis by tandem mass spectrometry. The Cellular Imaging Core focuses on classic neuropathology (light and EM), immunohistochemistry, and innovative techniques such as confocal microscopy. The Neuroimaging Core provides access to structural and functional brain imaging and image processing. The Biostatistics and Informatics Core assists investigators in study development, use of statistical methodology, and data storage management and analysis. Finally, the Neurobehavioral Evaluation Core provides support for neuropsychological testing and development of behavioral tasks for functional imaging. With the continued support of the MRDDRC, we expect to further enhance research productivity in the area of intellectual and other developmental disabilities.